Background: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from dysfunction of the protein myotubularin encoded by the gene. XLMTM has a high neonatal and infantile mortality rate due to a severe myopathic phenotype and respiratory failure. However, in a minority of XLMTM cases, patients present with milder phenotypes and achieve ambulation and adulthood. Notable facial dysmorphia is also present.
Methods: We investigated the genotype-phenotype correlations in newly diagnosed XLMTM patients in a patients' cohort (previously published data plus three novel variants, = 414). Based on the facial gestalt difference between XLMTM patients and unaffected controls, we investigated the use of the Face2Gene application.
Results: Significant associations between severe phenotype and truncating variants ( < 0.001), frameshift variants ( < 0.001), nonsense variants ( = 0.006), and in/del variants ( = 0.036) were present. Missense variants were significantly associated with the mild and moderate phenotype ( < 0.001). The Face2Gene application showed a significant difference between XLMTM patients and unaffected controls ( = 0.001).
Conclusions: Using genotype-phenotype correlations could predict the disease course in most XLMTM patients, but still with limitations. The Face2Gene application seems to be a practical, non-invasive diagnostic approach in XLMTM using the correct algorithm.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10742680 | PMC |
http://dx.doi.org/10.3390/genes14122174 | DOI Listing |
Acta Neuropathol Commun
December 2024
Institute of Myology, Neuromuscular Morphology Unit, Sorbonne Université, INSERM, GHU Pitié-Salpêtrière, Paris, France.
Neuromuscular disorders (NMD) with neonatal or early infantile onset are usually severe and differ in symptoms, complications, and treatment options. The establishment of a diagnosis relies on the combination of clinical examination, morphological analyses of muscle biopsies, and genetic investigations. Here, we re-evaluated and classified a unique collection of 535 muscle biopsies from NMD infants aged 0-6 months examined over a period of 52 years.
View Article and Find Full Text PDFZhonghua Yi Xue Yi Chuan Xue Za Zhi
December 2024
Fujian Children's Hospital (Shanghai Children's Medical Center Fujian Hospital), Fuzhou, Fujian 350011, China.
Cells
November 2024
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U1258, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.
Store-operated Ca entry (SOCE) controls Ca homeostasis and mediates multiple Ca-dependent signaling pathways and cellular processes. It relies on the concerted activity of the reticular Ca sensor STIM1 and the plasma membrane Ca channel ORAI1. STIM1 and ORAI1 gain-of-function (GoF) mutations induce SOCE overactivity and excessive Ca influx, leading to tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness and a variable occurrence of multi-systemic anomalies affecting spleen, skin, and platelets.
View Article and Find Full Text PDFInt J Med Sci
September 2024
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Myofibrillar myopathy (MFM) is a group of hereditary myopathies that mainly involves striated muscles. This study aimed to use tandem mass tag (TMT)-based proteomics to investigate the underlying pathomechanisms of two of the most common MFM subtypes, desminopathy and titinopathy. Muscles from 7 patients with desminopathy, 5 with titinopathy and 5 control individuals were included.
View Article and Find Full Text PDFJ Physiol
October 2024
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB-NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super-relaxed state was significantly impaired in NEB-NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small-molecule Mavacamten is known to promote the myosin super-relaxed state and reduce the ATP demand, we tested its potency in the context of NEB-NM.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!